"Inflammatory interstitial nephritis is an important cause of both acute and chronic renal failure and of acknowledged significance in the decline in glomerular filtration rate accompanying primary glomerular disease. The major focus in her laboratory is on delineating the mechanisms by which T lymphocytes initiate and amplify injury to the interstitium of the kidney. In this proposed renewal, their efforts will be focused on two distinct receptor/ligand systems which have significant effects on T cell function. The first system will be the alpha-beta heterodimeric T cell antigen receptor. They will comprehensively define the V-beta regions which undergo clonal expansion in rats immunized to produce autoimmune interstitial nephritis. These studies will utilize a panel of rat V-beta specific primers to screen kidney-infiltrating lymphocytes, segregated by CD4/CD8 phenotype, by reverse transcription-polymerase chain reaction for relative expression of V-beta families 1-20 and compare this to peripheral lymphocytes. They will perform this analysis on diseased kidneys at both an acute and chronic phase of disease. Based on the V-beta regions used and junctional sequences, they will then design TCR-beta chain peptides, examine their immunogenicity in the Brown Norway rat, and finally test the efficacy of immunization with such peptides in improving the histologic and functional parameters of autoimmune interstitial nephritis. The second receptor-ligand couple they will study is that of CD40 and the CD40L (gp39). The CD40L is expressed on the T cell surface only transiently following activation. CD40 expression has been best characterized on B cells. The interaction of these two cell surface molecules is critical for T cell induced B cell differentiation, yet little is known about the effect of this interaction on the T cell. In preliminary studies, they have found that (CD40L antibodies block proliferation of nephritogenic T cell clones, IL-2 generation, and histologic disease expression following immunization. Their proposed studies will utilize well-characterized nephritogenic murine T cell clones, and the in vivo model of interstitial nephritis to delineate how disrupting the CD40-CD40L interaction aborts T cell activation in vitro and the expression of a kidney specific autoimmune disease.